Researchers funded in part by the National Institutes of Health have identified the gene that accounts for most cases of Goltz syndrome, a rare skin disorder that can also affect bone and eye development.

The cases appear to result from a defect in the gene known as PORCN, which contains the information needed to make a protein, referred to by researchers as porcupine. The Porcupine protein, which was first identified in fruit flies, was named for the pattern of spikes projecting from skin cells of the larval fly’s body, bearing a resemblance to the quills of a porcupine.

“Identifying a genetic mutation for Goltz syndrome is a critical first step in understanding and eventually treating the condition,” said Duane Alexander, director of the National Institute of Child Health and Human Development, the NIH institute that provided funding for the Mental Retardation and Developmental Disabilities Research Center at Baylor College of Medicine, where the study was conducted.

The study was lead jointly by Xiaoling Wang, Department of Obstetrics and Gynecology at Baylor College of Medicine, and V. Reid Sutton, Department of Molecular and Human Genetics at Baylor College of Medicine.

The findings were published online in Nature Genetics.

Goltz syndrome, also called focal dermal hypoplasia, causes a distinctive red rash and thinning of the skin, which allows fat from the tissue below to protrude and form small yellowish-white lumps.

The disorder often causes brittle hair and nails, and deformities in the hands, such as extra, missing, or deformed fingers. Individuals with Goltz syndrome can also have missing or underdeveloped eyes. In addition, the disorder can affect the stomach, intestines, heart, lungs, and kidneys, said Dr. Ignatia B. Van den Veyver, associate professor at Baylor College of Medicine’s Departments of Obstetrics and Gynecology and of Molecular and Human Genetics and the senior author of the paper. Mental retardation is seen in about fifteen percent of patients with Goltz syndrome.

Because 90 percent of Goltz syndrome cases are seen in females, the disorder was believed to be caused by a gene on the X chromosome. After analyzing the genes of two girls with Goltz syndrome, the researchers found that both patients were missing a portion of the X chromosome where seven genes are located. Of the missing seven, the researchers learned that Goltz syndrome resulted from an absence of the PORCN gene, said Dr. Van den Veyver.

The PORCN gene is active in the embryo and fetus, creating proteins important in the development of the skin, skeleton, and eyes — all affected in the disorder.

Researchers then did genetic analyses of 15 girls with Goltz syndrome and found that the PORCN gene was affected in 10 of them.

Although the PORCN gene has been studied in mice and fruit flies, very little is known about the gene’s function in humans, said Dr. Van den Veyver. The mouse and Drosophila porcupine proteins are known to be important for the secretion of Wnt proteins from the cells that produce them. Wnt proteins are involved in early development. They interact with other proteins within the cell to begin the complex chain of events leading to the development and differentiation of organ systems in early life.

This discovery may lead to greater understanding of the function of Wnt proteins in humans, said Dr. Van den Veyver.

By identifying the genetic defect which causes Goltz syndrome, it may be possible to understand more of the processes critical for skin, eye and bone development, she said.

“The findings are important because they offer insight into a developmental disorder that was previously little understood,” said Ljubisa Vitkovic, M.D., of NICHD’s Mental Retardation and Developmental Disabilities Branch. “But they also illustrate how a mutation in the human counterpart of a protein known to regulate development in flies and mice can affect the skin and other human organs.”